Background: Invasive breast carcinoma expressing estrogen receptor (ER) at low levels by immunohistochemistry (IHC) constitute a minority of ER positive tumors. Clinically these tumors are considered within in the umbrella group of ER positive breast cancers. However, recent studies have shown the clinical significance of semi-quantitative hormone receptor levels and it is possible that these “low ER positive” tumors are different from the usual ER positive tumors.Design: Of the 731 total ER positive invasive breast cancers in the year 2010 at our institution, 53 (7.3%) cases had H-scores of 1-100, which was used as the definition of “low ER positive” cases. HER2 positive cases were excluded from this analysis. A total of 38 ER+/HER2 negative cases were analyzed for various morphologic parameters including tumor border, overall grade and mitotic activity. The following features were considered present if identified in ≥10% of the tumor: sheet-like growth pattern, spindle cells, apocrine differentiation, intra-tumoral lymphocytic infiltrate, and necrosis. Nucleoli were considered prominent if visible at 10X objective and substantial apoptosis was considered present if easily visible at 10X. Cell proliferative activity was assessed by Ki-67 labeling index (LI). Neoadjuvant therapy (NAT) was administered in 12 cases which made it possible to assess pathologic complete response rate in these low ER+/HER2 negative tumors.Results: The average age of the patients was 57 years. The mean tumor size was 2.0 cm. Most (37 cases, 97%) tumors were of ductal no special type carcinoma, and one (3%) was a pleomorphic lobular carcinoma. Twenty-eight (74%) carcinomas were grade 3 with average mitotic count of 23 mitotic figures/10 hpf. The mean Ki-67 LI was 73%. The tumors showed circumscribed borders in 42%, sheet-like growth pattern in 71%, spindle cells in 29%, apocrine differentiation in 26%, prominent nucleoli in 47%, lymphocytic infiltrate in 58%, necrosis in 39% and apoptosis in 15% cases. Lymphovascular space invasion was noted in 29% and positive lymph nodes in 38% cases. Of the 38 cases 35 (92%) were negative for progesterone receptor. Pathologic complete response (pCR) was seen in 4 of 12 cases (33%) that received NAT. The average tumor volume reduction in cases that failed to achieve pCR was 71%.Conclusions: Low ER+/HER2 negative breast cancers have morphologic features and a response to chemotherapy more similar to triple negative tumors rather than the usual type of ER positive tumors. These tumors form a distinct group within ER positive breast cancers.Category: Breast